Seyschab H, Sun Y, Friedl R, Schindler D, Hoehn H
Institut für Humangenetik, Universität Würzburg, Germany.
Hum Genet. 1993 Aug;92(1):61-8. doi: 10.1007/BF00216146.
The predominant cell cycle change induced by X-rays and clastogens in peripheral blood mononuclear cells is the accumulation of cells in the G2 phase of the cell cycle. We show that this accumulation consists of cells that are either delayed or arrested within the G2 phase. Since both X-rays and DNA crosslinking chemicals are known to damage DNA, the G2 phase inhibition caused by these agents is thought to be one of the primary manifestations of (unrepaired) DNA damage. This interpretation is supported by two additional findings. (1) Older individuals have elevated baseline levels of mononuclear blood cells that are delayed and/or arrested in the G2 phase of the cell cycle. This coincides with the increased chromosomal breakage rates reported for older individuals. (2) Irrespective of their age, individuals with inherited genetic instability syndromes (such as Fanconi anemia and Bloom syndrome) exhibit elevated G2 phase cell fractions. We show that the method used to detect such induced or spontaneous cell cycle changes, viz. BrdU-Hoechst flow cytometry, is a rapid and highly sensitive technique for the assessment of genetic cell damage.
X射线和断裂剂在外周血单个核细胞中诱导的主要细胞周期变化是细胞在细胞周期的G2期积累。我们发现这种积累包括在G2期延迟或停滞的细胞。由于已知X射线和DNA交联化学物质都会损伤DNA，因此这些因素导致的G2期抑制被认为是（未修复的）DNA损伤的主要表现之一。另外两个发现支持了这一解释。（1） 老年人外周血单个核细胞在细胞周期G2期延迟和/或停滞的基线水平升高。这与报道的老年人染色体断裂率增加相一致。（2） 无论年龄大小，患有遗传性基因不稳定综合征（如范可尼贫血和布卢姆综合征）的个体G2期细胞比例都会升高。我们表明，用于检测这种诱导或自发细胞周期变化的方法，即BrdU-Hoechst流式细胞术，是一种评估遗传细胞损伤的快速且高度灵敏的技术。
